5GO4

Truncated mitofusin-1, nucleotide-free

5GO4 の概要

• エントリーDOI: 10.2210/pdb5go4/pdb
• 関連するPDBエントリー: 5GOE 5GOF 5GOM
• 分子名称: Mitofusin-1 (2 entities in total)
• 機能のキーワード: hydrolase, mitochondrial fusion
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Mitochondrion outer membrane ; Multi- pass membrane protein . Isoform 2: Cytoplasm: Q8IWA4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48417.09

構造登録者

Cao, Y.L.,Gao, S. (登録日: 2016-07-26, 公開日: 2017-01-25, 最終更新日: 2024-03-20)

主引用文献

Cao, Y.L.,Meng, S.,Chen, Y.,Feng, J.X.,Gu, D.D.,Yu, B.,Li, Y.J.,Yang, J.Y.,Liao, S.,Chan, D.C.,Gao, S.
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion
Nature, 542:372-376, 2017

PubMed Abstract: Mitochondria are double-membraned organelles with variable shapes influenced by metabolic conditions, developmental stage, and environmental stimuli. Their dynamic morphology is a result of regulated and balanced fusion and fission processes. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and the maintenance of membrane potential. Mitofusins are dynamin-related GTPases that are essential for mitochondrial fusion. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via combined oligomerization and GTP hydrolysis. However, the molecular mechanisms of this process remain unknown. Here we present crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of MFN1 and resembles the 'neck' of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote GTPase domain dimerization in the transition state. Disruption of GTPase domain dimerization abolishes the fusogenic activity of MFN1. Moreover, a conserved aspartate residue trigger was found to affect mitochondrial elongation in MFN1, probably through a GTP-loading-dependent domain rearrangement. Thus, we propose a mechanistic model for MFN1-mediated mitochondrial tethering, and our results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders.

PubMed: 28114303
DOI: 10.1038/nature21077

実験手法

X-RAY DIFFRACTION (2.202 Å)